1. Field of Invention
This invention relates to intermediate compounds and processes for the production of compounds useful for the preparation of renin inhibitors.
2. Information Disclosure
The renin angiotensin system is an important vasoconstrictor mechanism, and is implicated in hypertension. The end-product of this system is angiotensin II which is among the most powerful vasoconstrictor agents known. Angiotensin II is produced in a two-step process from angiotensinogen as follows: EQU Angiotensinogen.fwdarw.angiotensin I.fwdarw.angiotensin II.
The conversion of angiotensinogen to angiotensin I is catalyzed by renin. [For review, see M. A. Ondetti and D. W. Cushman, "Enzymes of the Renin Angiotensin System and Their Inhibitors", Ann. Rev. Biochem., 51, pp. 283-308 (1982)].
To prevent the hypertensive effect of the renin-angiotensin system it would be useful to have effective renin inhibitors. Renin inhibitors are known [e.g., European patent publication, EP No. 0118223, and U.S. Pat. Nos. 4,481,192, 4,424,207 and 4,477,449]. By preventing or controlling the formation of angiotensin I from angiotensinogen with these renin inhibitors it may be possible to control unwanted levels of subsequent deleterious substances such as angiotensin II. Therefore, renin inhibitors are potentially useful for diagnosis and treatment of renin dependent hypertension and for the treatment of congestive heart failure. Renin inhibitors may also be useful in combination with other therapeutic agents such as diuretics (e.g., hydrochlorothiazide and furosemide), and vasodilators (e.g. minoxidil).
The background for the incorporation of the intermediate compounds of the instant invention into renin inhibitors can be found in U.S. patent application Ser. No. 663,027, filed on Oct. 19, 1984, which is a continuation-in-part of application Ser. No. 638,025, filed Aug. 6, 1984, and in European patent publication EP No. 0118223.
EP No. 0118223 also refers to the preparation of compounds related to the compounds of the instant application such as (3S,4S)-3-[(benzyloxycarbonyl)amino]-4-[(tert-butoxycarbonyl)amino]-6-meth ylheptanoic acid. No experimental details of the synthesis are reported therein.
P. G. Mattingly et al., J. Am. Chem. Soc., 101, p. 3983 (1979) refers to cyclization of amides to .beta.-lactams utilizing triphenylphosphine and DEAD. A method for reducing the .beta.-lactam so produced is referred to in P. G. Mattingly and M. J. Miller, J. Org. Chem., 45, p. 410 (1980).
D. M. Floyd et al., J. Org. Chem., 47, p. 5160 (1982) refers to amide cyclization utilizing potassium carbonate to produce an azetidinone and reduction thereof.
D. F. Veber et al., Trans. Biochem. Soc., 12, p. 956 (1984) and M. G. Bock et al., [J. Chem. Soc. Chem. Comm., p. 109 (1985) refer to the preparation of 2-alkylated statine analogues and their incorporation into peptidic renin inhibitors.
None of the documents cited above teaches or suggests the preparation of the substituted 3,4-diamino pentanoic acid derivatives of the instant application and the intermediate compounds and processes useful in the preparation thereof.